Yue Yu1, Ou Yang1,2, Ladan Fazli1, Paul S Rennie1, Martin E Gleave1, Xuesen Dong1,3. 1. Department of Urologic Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada. 2. The First Hospital, Jilin University, Jilin Province, China. 3. Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Canada.
Abstract
BACKGROUND: The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer-associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated. METHODS: Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration-resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α-SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells. RESULTS: PR protein levels decreased in cancer-associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors progressed to the castration-resistant stage. Enhanced PR expression in human prostate stromal cells increased α-SMA, but decreased vimentin and FSP protein levels ligand-independently. CONCLUSION: These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression.
BACKGROUND: The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer-associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated. METHODS: Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration-resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α-SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells. RESULTS: PR protein levels decreased in cancer-associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors progressed to the castration-resistant stage. Enhanced PR expression in human prostate stromal cells increased α-SMA, but decreased vimentin and FSP protein levels ligand-independently. CONCLUSION: These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression.
Authors: Halema Al-Farsi; Iman Al-Azwani; Joel A Malek; Lotfi Chouchane; Arash Rafii; Najeeb M Halabi Journal: J Transl Med Date: 2022-05-26 Impact factor: 8.440
Authors: Thomas Gevaert; Yves-Rémi Van Eycke; Thomas Vanden Broeck; Hein Van Poppel; Isabelle Salmon; Sandrine Rorive; Frank Claessens; Dirk De Ridder; Christine Decaestecker; Steven Joniau Journal: Sci Rep Date: 2018-09-25 Impact factor: 4.379